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Infections

Safety of voriconazole and sirolimus coadministration after allogeneic hematopoietic SCT

Bone Marrow Transplantation volume 50, pages 438–443 (2015)Cite this article

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Abstract

Antifungal prophylaxis with azoles is considered standard in allogeneic hematopoietic SCT (allo-HSCT). Although sirolimus is being used increasingly for the prevention of GVHD, it is a substrate of CYP3A4, which is inhibited by voriconazole, and concurrent administration can lead to significantly increased exposure to sirolimus. We identified 67 patients with hematologic malignancies who underwent allo-HSCT with sirolimus, tacrolimus and low-dose MTX and received concomitant voriconazole prophylaxis from April 2008 to June 2011. All patients underwent a non-myeloablative or reduced-intensity conditioned allo-HSCT. Patients received sirolimus and voriconazole concurrently for a median of 113 days. The median daily dose reduction of sirolimus at the start of coadministration was 90%. The median serum sirolimus trough levels before and at steady state of coadministration were 5.8 ng/mL (range: 0–47.6) and 6.1 ng/mL (range: 1–14.2) (P=0.45), respectively. One patient with an average sirolimus level of 6 ng/mL developed sirolimus-related thrombotic microangiopathy that resolved after sirolimus discontinuation. No sinusoidal obstructive syndrome was reported. Seventeen patients (25%) prematurely discontinued voriconazole because of the adverse events. Only two patients (3%) presented with possible invasive fungal infections at day 100. We demonstrate that sirolimus and voriconazole coadministration with an empiric 90% sirolimus dose reduction and close monitoring of sirolimus trough levels is safe and well tolerated.

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Acknowledgements

We gratefully acknowledge the expert care provided to our patients by the fellows, physician assistants, nurse practitioners and nurses of Memorial Sloan Kettering Cancer Center.

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Author notes

  1. I Ceberio and K Dai: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medicine, Adult Bone Marrow Transplantation Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    I Ceberio, J N Barker, H Castro-Malaspina, J D Goldberg, S Giralt & M-A Perales

  2. Department of Hematology, Hospital Universitario Donostia, Donostia, Spain

    I Ceberio

  3. Pharmacy Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    K Dai & N G Adel

  4. Department of Biostatistics and Epidemiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    S M Devlin

  5. Weill Cornell Medical College, New York, NY, USA

    J N Barker, H Castro-Malaspina, J D Goldberg, S Giralt & M-A Perales

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  1. I Ceberio
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Correspondence to I Ceberio or M-A Perales.

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Competing interests

IC received research support from Pfizer Spain. M-AP has served on advisory boards for Astellas and Merck. The remaining authors declare no conflict of interest.

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Ceberio, I., Dai, K., Devlin, S. et al. Safety of voriconazole and sirolimus coadministration after allogeneic hematopoietic SCT. Bone Marrow Transplant 50, 438–443 (2015). https://doi.org/10.1038/bmt.2014.286

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